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Hypopigmented lesions in early leprosy--a clinical and histological study.

26 Patients of leprosy presenting with hypopigmented lesions were divided on morphological grounds into 3 Sub groups, Group I (9 patients) with well-defined single patch with moderate to complete sensory loss; Group II (8 patients) with single ill-defined lesion having partial sensory loss; and Group III (9 patients) having multiple hypo-pigmented patches with mild to moderate sensory loss. Epidermal atrophy was a conspicuous histological finding in all groups. Only patients in Group I showed epitheloid cells in dermal infiltrate with erosion of epidermis in one case. This group may be labelled as maculoanesthetic leprosy. Patients in Group II and III showed mononuclear cell infiltrate in dermis, around neurovascular bundles and appendages. They were histologically consistent with indeterminate leprosy. Follow-up biopsy after six to eight months of treatment showed healing of the lesion of reduction in the infiltrate in most cases.

Adolescent↗

Adenosine deaminase activity in leprosy.

Adenosine deaminase (ADA) activity was studied in serum and peripheral blood lymphocytes of leprosy patients and healthy controls. Serum ADA levels were found to be elevated in tuberculoid as well as lepromatous cases compared to control subjects. Serum ADA activity was significantly higher in tuberculoid cases than in the lepromatous group. Lymphocyte adenosine deaminase activity showed a similar trend. These results suggest that, since the overall activity of the enzyme is not deficient in leprosy, the cellular immune abberation seen in the different types of leprosy may be due to abnormal proliferation of different subsets of lymphocytes in response to M. leprae.

Adenosine Deaminase↗

Clinical trial of pefloxacin and ofloxacin in the treatment of lepromatous leprosy.

Twenty-one previously untreated lepromatous patients were randomized into two groups and treated with either 800 mg pefloxacin (PEFLO) or 400 mg ofloxacin (OFLO) once daily. The trial consisted of two parts: monotherapy from day 0 to day 56; and combined with the World Health Organization multidrug therapy (WHO/MDT) regimen for multibacillary (MB) leprosy from day 57 to day 180. Four patients were removed from the trial because the organisms recovered from their pretreatment biopsies failed to infect mice. Among the remaining 17 cases, four (23.5%) had primary resistance to dapsone but all of them were susceptible to rifampin. The initial (day 0) proportion of viable organisms, as measured by mouse foot pad inoculation, varied tremendously from patient to patient despite randomization during admission. Definite clinical improvement was noticed in virtually all patients after 22 doses of treatment with either PEFLO or OFLO. A significant fall in the morphological index (MI) occurred as early as after 8 doses of PEFLO or after 22 doses of OFLO; the bacterial load also showed a moderate degree of reduction during the period of monotherapy. Although single-dose PEFLO or OFLO displayed only a modest degree of bactericidal effect against Mycobacterium leprae, about 99.9%, or 4 logs, of organisms viable on day 0 were killed by 22 doses of either PEFLO or OFLO. No significant difference in the therapeutic effect was detected between the two regimens. During PEFLO or OFLO monotherapy, except in one patient (case no. 10), the side effects were few and mild. Case no. 10 developed a psychic disorder after 27 days of PEFLO monotherapy, presumably due to the treatment with PEFLO. All of the patients tolerated the period of combined therapy extremely well, although some asymptomatic and transient laboratory abnormalities were observed. Because both PEFLO and OFLO displayed rapid bactericidal activities in human leprosy and were well tolerated by the patients, further clinical trials and field trials in evaluating the therapeutic effects of combined regimens containing both rifampin and PEFLO or OFLO are being organized. Since this is the first clinical trial in leprosy employing nude mice, in combination with normal mice, for monitoring the therapeutic effects of antimicrobials, the advantages, limitations and appropriate timing in using nude mice are discussed.

Adolescent↗

In vitro studies on dermal leprosy granulomas: assessment of division and protein synthesis of cells.

Single cell suspension from dermal leprosy granulomas (10 tuberculoid and 10 lepromatous) was prepared and an assessment of the division and protein synthesis by the cells was made. The cells of tuberculoid granulomas showed a high incorporation of 3H-thymidine and 14C-leucine. On the contrary, the cells of the lepromatous granulomas exhibited poor division but their protein synthesis remained unimpaired. These observations suggest that the epithelioid cell granuloma of tuberculoid leprosy appears to be more active and secretory than the macrophage granuloma of lepromatous leprosy.

Cell Division↗

Morphometric study of stratum corneum in leprosy.

Abnormalities in Stratum Corneum (SC) in leprosy lesions have been demonstrated as evidenced by poor hydration power of SC and increased SC turn-over. In continuation of the same study morphometric studies of the SC in leprosy was undertaken as per measurement of the Thickening of the SC, Mean epidermal thickness and Basal layer: Granular layer cell ratio (B : G ratio) of the H.E. stained tissues. Further, on freshly frozen tissues the SC cell-layers were also counted. The findings suggest increased proliferative activity of the epidermis which may lead to formation of defective SC in leprosy.

Adolescent↗

Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous leprosy patients.

It is conceivable that an abnormal expression of cell-adhesion molecules can contribute to the poor inflammatory response seen in some inflammatory skin diseases. Adhesins are cell-surface molecules that are expressed by many cell types. The main function of adhesins appears to be the promotion of cellular interactions, such as those occurring between immune cells. The epidermis of patients with inflammatory skin diseases exhibits an increased expression of ICAM-1, and it has been postulated that such increased expression can be important in the genesis of cutaneous inflammation. The expression of cell-adhesion molecules (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied, as well as the in vitro expression of these molecules induced with gamma interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in the nearly normal skin from these patients incubated with IFN-gamma. A similar expression of the four molecules studies was noted in the dermis of both the lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous leprosy patients appears to have a defective expression of ICAM-1.

Antigens, CD↗

[Sequential activation of cellular and humoral immunity in leprosy: considerations based on recent findings].

Lepromatous leprosy in the human being evolves showing a progressive loss of cell mediated immunity (CMI) to the antigens of Mycobacterium leprae (ML). This does not prevent the host to respond with antibodies to the same microorganism. On the other hand, the production of antibodies to the great majority of exogenous antigens results from cell-to-cell interactions that involve the participation of helper T cells. On this ground, a satisfactory explanation for the loss of CMI to M. leprae (which indicates either the loss or inactivation of specific helper T cells), with no effect on the humoral response to the same microorganism (this implying the participation of functional specific helper T cells), was difficult to found. It was not until Mosmann established, in the mouse, the existence of two subpopulations of helper T cells, that a feasible explanation for the apparent immunological paradox observed in leprosy was possible to offer. The work described here, based to a great extent in our experience on murine leprosy, refers to recent concepts concerning this issue.

Animals↗

Role of antineural antibodies in perpetuation of a pre-existing peripheral nerve damage in leprosy.

This study was carried out in order to find out whether antineural antibodies had a role to play in perpetuating pre-existing nerve damage in leprosy. Indirect ELISA was carried out on sera from 20 leprosy patients and five normal controls using antigen prepared from peripheral nerves of a cured bacteriologically negative leprosy patient. None of the patients had significant levels of IgG antibodies whereas eight of them (40%) had significant levels of IgM antibodies. However, there was no correlation with duration of disease, treatment received, nerve enlargement or active neuritis. The nature of these antibodies is discussed.

Adult↗

Effect of rhuIFN-gamma treatment in multibacillary leprosy patients.

Previous studies have shown that when multibacillary leprosy patients were treated with recombinant human interferon gamma (rhuIFN-gamma) for 6-10 months there was an accelerated reduction in the number of acid-fast bacilli in the skin at the site of injection as well as an accelerated bacillary reduction at distal sites. However, this favorable out-come of IFN-gamma treatment was associated with the development of erythema nodosum leprosum (ENL). The present study was undertaken to investigate whether rhuIFN-gamma-induced bacillary clearance could be disassociated from the induction of ENL. rhuIFN-gamma was administered together with thalidomide and conventional multidrug chemotherapy to newly diagnosed leprosy patients. During treatment with this combination of drugs, the mean reduction in bacterial load was the same as the reduction observed with chemotherapy alone. Moreover, the inclusion of thalidomide in the treatment regimen was associated with a low frequency of ENL episodes. A second group of leprosy patients, who had already completed 2 years of chemotherapy, were treated with rhuIFN-gamma only. In those patients who were skin bacilli negative, ENL did not occur during rhuIFN-gamma treatment. In contrast, in bacilli-positive patients the frequency of ENL during rhuIFN-gamma treatment was higher, as was the occurrence of local erythema and induration. However, rhuIFN-gamma treatment without concomitant chemotherapy did not result in a reduction in the bacterial load in the skin of bacilli-positive patients. These findings, taken together, indicate that rhuIFN-gamma does not, by itself, accelerate bacterial clearance, but requires concomitant chemotherapy to achieve the accelerated reduction in bacillary load. Thalidomide reduces the frequency of IFN-gamma-induced ENL, but also eliminates the IFN-gamma-induced bacillary clearance.

Clofazimine↗

Concurrent leprosy and HIV infection: a report of three cases.

Three cases of concurrent infection with HIV and leprosy are reported. One had developed borderline lepromatous leprosy one year after identifying HIV infection, while the other two had indeterminate leprosy and both conditions were identified at the same time in these two patients. All three cases showed satisfactory response to standard antileprosy multidrug therapy.

Adult↗

Production of host-protective (IFN-gamma), host-impairing (IL-10, IL-13) and inflammatory (TNF-alpha) cytokines by PBMC from leprosy patients stimulated with mycobacterial antigens.

The production of IFNgamma, IL-10, IL-13 and TNFalpha was determined using PBMC from 7 tuberculoid (TT) and 7 lepromatous leprosy (LL) patients, after stimulation with several mycobacterial antigens, in an attempt to characterize the cytokine responses to these antigens. The results showed that TT patients displayed higher IFNgamma levels than LL patients with the mycobacterial antigens tested, but no differences in IL-10 production were observed between the two groups. MLSC antigen was associated with the lowest IFNgamma production in TT and LL groups. Only BCG could be identified with stimulation of IFNgamma production in some LL patients. The mycobacterial antigens SP+, SP- and BCG were associated with higher TNFalpha production in patients and controls, suggesting that these antigens could be involved in immunopathological effects. Our findings showed that the antigens tested were associated with a heterogeneous cytokine production in leprosy patients. Further studies are required to establish if an individual antigen can be identified as inducing a protective immune response in leprosy.

Antigens, Bacterial↗

B7-1, but not CD28, is crucial for the maintenance of the CD4+ T cell responses in human leprosy.

We used human leprosy as a model to compare patterns of costimulatory molecule expression in respect to the clinical/immunologic spectrum of disease. We found that B7-1, B7-2, and CD28 transcripts dominated in tuberculoid leprosy patients, who have potent T cell responses to Mycobacterium leprae. In contrast, CTLA-4 was more strongly expressed in lesions from lepromatous patients, who manifest specific T cell anergy to the leprosy bacterium. T cell clones from tuberculoid lesions were CD4+CD28+ or CD4+CD28-, and T cell clones from lepromatous lesions were predominantly CD8+CD28-. The M. leprae-specific recall response of CD4+ T cell clones from tuberculoid lesions was blocked by anti-B7-1 mAb, but not by anti-B7-2 mAb or CTLA-Ig. However, anti-CD28 and anti-CTLA-4 mAbs did not block activation of clones from tuberculoid lesions, suggesting that B7-1 may utilize another costimulatory pathway. Peripheral blood T cell responses in the lepromatous form were strongly regulated by CD28 during T cell activation, in contrast to the tuberculoid form. Thus, B7-1 costimulation could play a role in maintaining a strong immune response to the pathogen.

Abatacept↗

Leprosy. Our Southeast Asian refugee experience.

In the past two years, we have diagnosed four cases of leprosy at the St Paul-Ramsey Hospital Dermatology Clinic. This is a markedly increased incidence for the state of Minnesota. All of these cases have been found among recently arrived Southeast Asian refugees not noted to have their disease by previous screening examinations. The purpose of this study is to report these four cases (two tuberculoid, one lepromatous, and one borderline leprosy) and to review the Southeast Asian Refugee Resettlement Program, focusing on medical screening programs. We recommend refugee health education, health personnel training, and refugee medical screening centers as ways to detect leprosy among refugees entering the United States.

Adult↗

Incidence of cancer in patients with leprosy.

Individuals with congenital immunodeficiences and patients who are immunosuppressed for maintenance of organ allografts experience a marked increase in the occurrence of malignancy. Patients with lepromatous leprosy also have depressed cellular immunity, but or study of 195 autopsied subjects with leprosy did not reveal an increase in the occurrence of cancer. Thirty-three of the 195 subjects with leprosy or 16.9% died of cancer, which is comparable to an age-matched group of individuals.

Adult↗

Pure neural leprosy: diagnostic value of the polymerase chain reaction.

Pure neural leprosy (PNL) is often difficult to diagnose when acid-fast bacilli (AFB) cannot be detected. We undertook the present study to evaluate use of the polymerase chain reaction (PCR) in diagnosing PNL. Fifty-eight patients (41 men and 17 women) suspected of pure neural leprosy (PNL) were examined. Patients were classified as borderline tuberculoid (BT, 40 cases) and polar tuberculoid (TT, 18 cases) types. Nerve biopsy was performed and was positive for AFB in 20 patients (all BT patients), i.e., 34.5% of total cases. DNA was extracted from the nerve biopsy samples and amplified using PCR for a specific repeated sequence of DNA from Mycobacterium leprae. PCR analysis was positive in the nerve samples from 29 patients (50%), 27 of the BT type, and 2 of the TT type patients. Further, PCR analysis was positive in 14 of 38 cases that were negative for AFB by nerve biopsy, of which 12 were of the BT type and 2 the TT type. PCR analysis proved to be a useful method to investigate pure neural leprosy, enabling confirmation of the diagnosis in more than a third of the cases that were negative for AFB by nerve biopsy.

Adult↗

Time-related decrease of substance P and CGRP in central and peripheral projections of sensory neurones in Mycobacterium leprae infected nude mice: a model for lepromatous leprosy in man.

We have previously shown the depletion of cutaneous calcitonin gene-related peptide (CGRP)- and substance P-containing nerves in human leprosy. The aims of this study were to investigate the temporal effects of leprosy on nerves in skin and spinal cord. Tissues were taken from nude mice, 6 and 12 months after inoculation of Mycobacterium leprae into the hind footpads, and from age-matched controls. Sections were immunostained with antisera to substance P or CGRP. After 6 months of infection, substance P- and CGRP-immunoreactive nerves were reduced in skin from all body areas; by 12 months, the reduction was substantially greater. In the spinal cord, sensory fibres immunoreactive for substance P had decreased compared with controls at 6 and 12 months [by 60 per cent (0.022 mm2) and 80 per cent (0.048 mm2), respectively, P less than 0.001], as with CGRP [30 per cent (0.018 mm2) (P less than 0.02) and 40 per cent (0.028 mm2) (P less than 0.01), respectively]. CGRP immunoreactivity was completely absent in motor neurones after 12 months of infection. Loss of CGRP- and substance P-immunoreactive fibres in skin and spinal cord, and CGRP in motor neurones is in accord with impaired pain sensation and muscle weakness in leprosy.

Animals↗

Anti-hapten antibodies and autoantibodies in Japanese patients with lepromatous leprosy.

In the sera of patients with lepromatous leprosy anti-DNP antibodies were detected in order to determine the mode of polyclonal B-cell activation. Anti-DNP antibodies were found in 30% of the patients with active lepromatous leprosy and in 8% of those with inactive lepromatous leprosy. The level of anti-DNP antibodies in active patients was significantly higher than the level in inactive patients and control. However, the presence of anti-DNP antibodies was unrelated to the production of circulating immune complexes and antinuclear antibodies. These results suggest that polyclonal B-cell activation might occur but that the B-cell clones stimulated by M. leprae are different from patient to patient.

Adult↗

Immunofluorescence studies across the leprosy spectrum.

Forty biopsies from skin lesions of untreated (24) and treated (16) leprosy patients, representing the whole leprosy spectrum, were examined by means of immunofluorescence (IF) methods. Only few or no cells staining with FTC-labelled antihuman immunoglobulin antisera were found in the lesional skin of all patients examined. Sparse IgM-deposits along the basement membrane of the epidermis were observed in a few borderline lepromatous and lepromatous patients. Complement deposits along the basement membrane of the epidermis and in the vessel walls were found in tuberculoïd as well as in lepromatous patients. Complement and in a lesser number IgG-deposits were observed around sweat glands and sometimes around sweat gland ducts and other skin appendages. Autofluorescing macrophages were noted in patients at the lepromatous side of the leprosy spectrum; approximately half of these patients showed complement deposits in an around these cells.

Complement System Proteins↗

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